By the late 1940s, Friendly was an experienced radio producer. It was in this role that Friendly (who had changed his name during his Providence days) first worked with Murrow on the Columbia Records historical albums, I Can Hear It Now. The first entry in the series, released on Thanksgiving Day 1948, covered the crisis and war years 1933–1945. It was a ground-breaker in that it used clips of radio news coverage and speeches of the major events from that twelve-year time span. Friendly created the concept after noticing the new use of audiotape in regular radio news coverage, as opposed to wire or disc recordings that were an industry standard. Nonetheless, Friendly periodically recreated the recordings of news events when such recordings didn't exist or were considered too chaotic to use on an album [1]. CBS correspondent David Schoenbrun, in his memoir On and Off the Air, said he once was forced by Friendly to ask Charles de Gaulle if he would recreate the speech he gave upon his return to Paris (de Gaulle refused). The recreations never were identified as such, and trying to separate the real from the recreated continues to be problematic for radio historians.

Although Murrow was an established CBS name and Columbia Records was then owned by CBS, Friendly's next full-time work came as a news producer at NBC. It was there that Friendly came up with the idea for the news-oriented quiz show Who Said That?, first hosted by NBC newsman Robert Trout, then Walter Kiernan, and John Charles Daly. The program, which Friendly edited, ran irregularly on NBC and then ABC between 1948 and 1955.[3]

After the success of The Quick and the Dead, Friendly was recruited to work full-time for CBS by news executive Sig Mickelson. That fall, Murrow and Friendly collaborated to produce a CBS Radio documentary series inspired by their record albums—a weekly show called Hear It Now that was hosted by Murrow. The show moved to television as See It Now on Sunday, November 18, 1951.

Murrow and Friendly broadcast a revealing See It Now documentary analysis on Senator Joseph McCarthy (airing March 9, 1954) that has been credited with changing the public view of McCarthy, and being a key event leading to McCarthy's fall from power. It was an extension of the duo's continuing probe of the conflict between McCarthy's anti-Communist crusade and individual rights.

Murrow and Friendly had produced a notable See It Now episode on the topic the previous fall, when the show probed the case of Air Force Reserve Lieutenant Milo Radulovich, who had lost his security clearance because of the supposed leftist leanings of his sister and father—evidence the Air Force kept sealed. Five weeks later, Radulovich was reinstated by the secretary of the Air Force. Radulovich was however granted leave of his duties that same year when he was forced to move temporarily to Phoenix, Arizona (USA) to care for his nephew who had recently been involved in a dog mauling incident.[4] After See It Now ended in the Summer of 1958, Murrow and Friendly worked together on its successor, CBS Reports, although Friendly alone was executive producer and Murrow no more than an occasional reporter and narrator. Their most famous CBS Reports installment—the probe of migrant farm workers Harvest of Shame—aired in November 1960 and still is considered one of television's finest single programs.

After Murrow's departure from the television network in 1961, Friendly continued to oversee several notable CBS Reports documentaries including Who Speaks for Birmingham?, Birth Control and the Law, and The Business of Heroin.

Under CBS president James T. Aubrey, Jr. the pressures on CBS News operations increased. Aubrey constantly fought with Friendly. Friendly felt Aubrey was insufficiently concerned with public affairs and in his memoir, Due to Circumstances Beyond Our Control, recounts one budget meeting at CBS when Aubrey talked at length of how much money the news was costing the company, a sea of red ink that could be stopped by replacing news with more entertainment programs. CBS founder and board chairman William S. Paley supported the news, however, and protected Friendly's division from Aubrey's proposed budget cuts.

In 1962, Aubrey ordered that there would be fewer specials, both entertainment and news, because he felt interruptions to the schedule alienated viewers by disrupting their routine viewing, sending them to the competition. Friendly resented this move. To Friendly's relief, in 1965 Aubrey was fired.

In 1966, Friendly resigned from CBS when the television network ran a scheduled episode of The Lucy Show instead of broadcasting live coverage of the first United States Senate hearings questioning American involvement in Vietnam.[6] Onetime CBS News president Dick Salant, the executive who preceded and later succeeded Friendly in the role, wrote in his memoirs that Friendly's problem was compounded by his inability to make such a request directly to the top CBS management (William S. Paley and Frank Stanton), as previous CBS News presidents had. In this case, Friendly had to go through a new executive level, through CBS Broadcast Group president Jack Schneider.

After he left CBS, Friendly initially worked as a broadcast consultant at the Ford Foundation, a position he maintained until 1980. In this capacity, he initially developed an infeasible plan to allocate revenue generated by communications satellites toward the nascent medium of public television before emerging as an integral figure in "negotiations about interconnection that would lead to the creation of the Public Broadcasting Service (PBS) in 1969"; by ensuring National Educational Television's subordination to the Washington-based PBS through the merger of NET with New York City's WNDT (including a $2 million Ford Foundation grant to bolster the station's local programming), Friendly reluctantly placated members of the Nixon administration who perceived NET as a propagandistic lodestar of the Eastern establishment.[7]

Despite his dearth of formal education—not atypical among contemporaneous practitioners—he was appointed to the faculty of the Columbia University Graduate School of Journalism as the tenured Edward R. Murrow Professor of Broadcast Journalism in 1966. By the time of his death in 1998, Friendly "was criticized by some working in network news as being isolated in academia and out of touch with the new realities—and limitations—of the business of broadcast journalism."[8] Nevertheless, over the next thirteen years, Friendly eclipsed top administrators (including Elie Abel, who was recommended by Friendly) in the popular consciousness due to his prominence at CBS and soon assumed stewardship of the school's hitherto threadbare broadcast journalism concentration. The non-degree Summer Program in Journalism for Members of Minority Groups (renamed the Michele Clark Fellowship Program for Minority Journalists following the death of a distinguished alumna in a December 1972 airplane crash) was directed by Friendly from 1968 to 1975, enabling media-savvy attorney Geraldo Rivera—among others—to switch careers during the tempestuous epoch. However, a proposed "University Broadcast Laboratory" (an experimental Sunday news magazine initially proposed by Friendly in partnership with the Ford Foundation, Columbia and NET) only manifested in attenuated form as Public Broadcasting Laboratory from 1967 to 1969; administrative and content circumscriptions imposed by the University trustees precipitated his divestiture from the program and hastened the retirement of Journalism School dean Edward W. Barrett. As chair of Mayor John Lindsay's Task Force on CATV and Telecommunications in 1968, he revived his revenue-sharing proposal by advising cable companies to set aside two channels that the public could lease for a minor fee, presaging the development of public-access television.

Spurred by classroom discussions, he inaugurated the Media and Society Friendly Seminars under the auspices of the Journalism School in 1974 as private conference fora on media, law (particularly the Constitution and the First Amendment), and public policy for the edification of professionals from disparate fields; drawing upon the case-oriented methodology employed by many professional schools and the Socratic method for interlocution, these eventually metamorphosed into PBS' long-running Fred Friendly Seminars in 1981.

Following his statutory retirement in 1979, Friendly relinquished control of the Journalism School's broadcast program; however, he continued to teach and produce the Seminars at Columbia in an emeritus capacity before retiring in earnest in 1992. The broadcast newsroom and an endowed professorship remain named for Friendly, attesting to his outsized influence at a critical juncture in the School's development.

He was the author of several books, including The Good Guys, The Bad Guys, And The First Amendment (an account of a number of First Amendment court cases and particularly of the Fairness Doctrine), Minnesota Rag (a history of Near v. Minnesota), The Constitution: That Delicate Balance, and Due to Circumstances Beyond Our Control (a memoir about his sixteen years at CBS).